CN120641145A - Biomaterial composition for tissue repair comprising a mixture of DNA fragments and polyols - Google Patents

Abstract

The present disclosure provides a composition for tissue repair, comprising a mixture of DNA fragments and a C3 or C4 polyol; a filler composition; a method for repairing tissue using the composition; and use of the composition in tissue repair.

Description

Tissue repair biomaterial composition comprising a mixture of DNA fragments and a polyol

[ Field of technology ]

The present disclosure relates to compositions for tissue repair comprising a mixture of DNA fragments and a C3 or C4 polyol, filler compositions, methods of tissue repair using the compositions, and the use of the compositions in tissue repair.

[ Background Art ]

With increasing interest in combating aging, more and more procedures are being used to compensate for defects in the body, including joints, cardiovascular, skin, etc. For example, cosmetic surgery, which aims to improve wrinkles or other appearance conditions, is also one of them. In this regard, a method of injecting highly biocompatible materials has been frequently employed in recent years to replace damaged biological tissue and to increase the volume of a desired body area.

For example, there are filler compositions containing hyaluronic acid as a main component, but some hyaluronic acid fillers are difficult to inject into the skin due to their high viscosity and low elasticity, they do not maintain their injection form (shape) for a long period of time even if injected into the skin, and the shape retention period is short. To improve this, various compounds are being added (U.S. Pat. No. 11,154,481), but it is difficult to improve the problem while minimizing side effects.

[ Invention ]

[ Problem ]

There remains a need to develop improved biomaterials for tissue repair.

[ Technical solution ]

It is an object of the present disclosure to provide a composition for tissue repair comprising a mixture of DNA fragments and a C3 or C4 polyol, wherein the content of the mixture of DNA fragments is in an amount of 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is in an amount of 0.5 wt% to 4 wt% relative to the total weight of the composition.

It is another object of the present disclosure to provide a filler composition comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is in an amount of 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is in an amount of 0.5 wt% to 4 wt% relative to the total weight of the composition.

It is another object of the present disclosure to provide a method of repairing tissue comprising the step of administering the tissue repair composition or filler composition to a subject.

It is another object of the present disclosure to provide a composition for tissue repair comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is in an amount of 2 wt% to 5wt% relative to the total weight of the composition, and the content of the polyol is in an amount of 0.5 wt% to 4 wt% relative to the total weight of the composition.

[ Technical Effect ]

The biological material for tissue repair has not only the capability of repairing tissues, but also a moisturizing effect, thereby having the effect of not giving dry feel to the tissues.

[ Brief description of the drawings ]

FIG. 1 shows the results of verifying the effect of increasing moisture content by animal experiments;

FIG. 2 shows the standardized results of the injection force test of the prepared comparative examples and examples;

FIGS. 3-6 show the phase angle test results of the comparative examples and examples prepared;

FIG. 7 shows the results of the biodegradability test of the comparative examples and examples prepared;

FIG. 8 shows the results of comparing the height and breadth of the injection site after injecting the prepared liquid compositions of the comparative example and example, and

Fig. 9 shows the results of comparing the properties of each composition when preparing the liquid composition.

[ Detailed description of the preferred embodiments ]

The present disclosure is described in detail below. Meanwhile, each of the descriptions and embodiments disclosed in the present disclosure may be applicable to other descriptions and embodiments as well. That is, all combinations of the various elements disclosed in the disclosure are within the scope of the disclosure. Furthermore, the scope of the present disclosure is not limited by the following detailed description. In addition, many papers and patent documents are referred to and cited in this specification. The disclosures of the cited papers and patent documents are incorporated by reference in their entireties to further clarify the level and scope of the subject matter to which this disclosure relates.

One aspect of the present disclosure provides a composition for tissue repair comprising a mixture of DNA fragments and an alcohol. In particular, the alcohol may be a polyol, more particularly a C3 or C4 polyol.

In one embodiment, the tissue repair composition of the present disclosure is characterized by comprising a mixture of DNA fragments and a C3 or C4 polyol as active ingredients.

As used herein, the term "DNA fragment mixture" includes DNA corresponding to a biopolymer consisting of phosphoric acid, four bases, and deoxyribose, and refers to a mixture of nucleic acid fragments that exist having a molecular weight within a predetermined range while being present as a nucleotide polymer. The DNA fragment mixture may exist in a mixed form of fragments having a relatively low molecular weight, but is not limited thereto, and may be used interchangeably with terms "DNA fragment", "DNA component", "nucleic acid fragment" and "nucleic acid fragment mixture".

In one embodiment, the DNA fragment mixture of the present disclosure may be a Polynucleotide (PN), a Polydeoxyribonucleotide (PDRN), or a mixture thereof.

As used herein, the term "polynucleotide" is referred to as "PN" and may refer to a DNA or RNA strand, which is a polymer of nucleotides in which nucleotide units (monomers) are linked together in a chain by covalent bonds. Furthermore, as used herein, the term "polydeoxyribonucleotide" is referred to as "PDRN" and may be a type of low molecular weight DNA complex having a specific molecular weight, but is not limited thereto. For example, polynucleotides may have a relatively longer nucleic acid length or a larger molecular weight than polydeoxyribonucleotides, which may be used as a raw material for medical devices, have a physical supporting effect of cell fixation and lubrication buffer, and may be used as a medical raw material for cell proliferation and tissue regeneration, but are not limited thereto.

In one embodiment, the liquid composition of the DNA fragment mixture of the present disclosure may include a buffer solution, and the above buffer solution may be any one or more selected from sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dodecahydrate, sodium chloride, magnesium chloride, potassium chloride and phosphate buffered saline, or N- (2-hydroxyethyl) -piperazine-N' -2-ethane sulfonic acid (HEPES), but is not limited thereto.

The mixture of DNA fragments according to any of the above embodiments may be obtained by extraction from the testes or semen of fish. In particular, such fish may be salmon. More specifically, it may be salmon or trout, but is not limited thereto.

The DNA fragment mixture according to any of the above embodiments may have a molecular weight of about 1kDa to about 100,000kDa, about 5kDa to about 50,000kDa, about 50kDa to about 10,000kDa, or about 50kDa to about 1,500kDa.

In any of the above embodiments, the DNA fragment mixture of the present disclosure may be a Polynucleotide (PN), but is not limited thereto.

The content of the DNA fragment mixture according to any of the above embodiments may be 2 wt% to 7 wt%, particularly 2 wt% to less than 7 wt%, 2 wt% to 6 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 7 wt%, 3 wt% to less than 7 wt%, 3 wt% to 6 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, 4 wt% to 7 wt%, 4 wt% to less than 7 wt%, 4 wt% to 6 wt%, 4 wt% to 5 wt%, 5 wt% to 7 wt%, 5 wt% to less than 7 wt%, 5 wt% to 6 wt%, 6 wt% to 7 wt%, or 6 wt% to 7 wt% with respect to the total weight of the tissue repair composition.

The C3 or C4 polyols of the present disclosure refer to alcohols having 3 or 4 carbon atoms with two or more hydroxyl groups (-OH) at the same time.

The content of the polyhydric alcohol according to any of the above embodiments may be 0.5 to 8 wt%, particularly 0.5 to 8 wt%, 1 to 3 wt%, 1 to 6 wt%, 1 to 5 wt%, 2 to 8 wt%, 2 to 6 wt%, 2 to 5 wt%, 2 to 4 wt%, 2 to 3 wt%, 0.5 to 2 wt%, 0.5 to 1 wt%, 1 to 8 wt%, 1 to 7 wt%, 1 to 6 wt%, 1 to 4 wt%, 1 to 3 wt%, 1 to 2 wt%, 2 to 8 wt%, 2 to 7 wt%, 2 to 5 wt%, 2 to 4 wt%, 3 to 3 wt%, 3 to 6 to 4 wt%, 4 to 6 wt%, or 4 to 3 wt%, with respect to the total weight of the tissue repair composition.

The polyol according to any one of the above embodiments may be any one or more selected from the group consisting of glycerol, propylene glycol, and butylene glycol, but is not limited thereto.

In the present disclosure, it has been confirmed that the polyhydric alcohol alone cannot be used for tissue repair purposes, and the combination of the DNA fragment mixture and the C3 or C4 polyhydric alcohol may reduce the viscosity, thereby increasing the convenience of injection.

In addition, the combination of the DNA fragment mixture with polyols such as polyethylene glycol (PEG) and triethylene glycol produces a large amount of foam during the preparation of its liquid composition, which increases the probability of defective products occurring during future product production, or a viscosity approaching 0, rendering it unusable for tissue repair. In contrast, the combination of the DNA fragment mixture of the present disclosure and the C3 or C4 polyol has been demonstrated to have a significantly lower probability in the above-described aspects.

Meanwhile, the composition for tissue repair of the present disclosure may have a tissue moisturizing ability.

As used herein, the term "tissue moisturizing ability" refers to increasing the moisture content of tissue. The tissue moisturizing ability of the present disclosure may mean that the moisture content of the tissue is increased when the composition of the present disclosure is injected into the tissue as compared to the moisture content when the composition of the present disclosure is not injected into the tissue. This ability to preserve moisture may facilitate tissue repair, have high implantation rates and moisturizing effects, while increasing the moisture content in the tissue, does not give dry feel to surrounding tissue, but rather relieves dry feel.

The composition for tissue repair according to any one of the above embodiments may increase the moisture content of the tissue upon injection of the tissue.

Examples of such tissues may include, but are not limited to, skin.

In one embodiment of the present disclosure, it was confirmed that a tissue repair composition further comprising a C3 or C4 polyol (in particular, at a specific content) not only has an excellent tissue repair effect, but also increases the moisture content when injected into a tissue as compared to a DNA fragment mixture comprising alone. This indicates that the composition of the present disclosure does not excessively absorb water from the surrounding tissue upon injection, provides water to the surrounding tissue, does not cause a dry feel to the surrounding tissue, but alleviates the dry feel, and has a tissue repair effect, a high implantation rate, and a good water content.

In particular, it was confirmed that when the composition comprises a mixture of DNA fragments and a C3 or C4 polyol (wherein the content of the mixture of DNA fragments is an amount of 2 to 5 wt% with respect to the total weight of the composition and the content of the polyol is an amount of 0.5 to 4 wt% with respect to the total weight of the composition), it is critical for moisturizing effect and the tissue repair effect is also very excellent within the same range. This indicates that the composition does not give a dry feel to the surrounding tissues but alleviates the dry feel within the range of the above-described content combination, has a tissue repair effect, and has a good moisturizing effect.

The composition for tissue repair according to any one of the above embodiments may include the DNA fragment mixture and the polyol in a weight ratio of 10:1 to 1:2, but is not limited thereto.

In any of the above embodiments, the tissue repair composition of the present disclosure may comprise the DNA fragment mixture and the polyol in a weight ratio of about 10:1 to about 1:2, about 10:1 to about 1:1, about 8:1 to about 1:1, about 6:1 to about 1:2, about 6:1 to about 1:1, about 5:1 to about 1:2, about 5:1 to about 1:1, about 4:1 to about 1:2, or about 4:1 to about 1:1, particularly in a weight ratio of about 10:1 to about 1:2, about 10:1 to about 1:1, or about 6:1 to about 1:2.

The term "about" may include not only the exact number recited after the term, but also ranges that are close or nearly so. Considering the context of the presentation of numbers, it may be determined whether any number is close or near to the particular number presented. For example, the term "about" may refer to a range of-10% to +10% of a given value. As another example, the term "about" may refer to a range of-5% to +5% of a given value. As another example, the term may be intended to include, but is not limited to, a range of + -0.5, + -0.4, + -0.3, + -0.2, + -0.1, etc.

In the present disclosure, even though the term "about" is omitted before a number, it is obvious that the present disclosure includes a range in which the term is not omitted.

Meanwhile, as used herein, the term "for tissue repair" means that it can be used to replace, repair and/or reconstruct human tissues and organs, such as blood vessels, heart, septum, fascia, and/or skin, etc.

The composition for tissue repair of the present disclosure is useful as a tissue repair biomaterial, and the tissue repair biomaterial refers to a biologically derived material for replacing, repairing and reconstructing human tissues and organs such as blood vessels, heart, septum, fascia, skin, etc., and is not limited to cosmetic fillers, possibly referring to a tissue repair biomaterial prescribed by the food and drug safety department.

The tissue repair composition of the present disclosure may be a liquid composition or an injectable composition, but is not limited thereto.

As used herein, the term "injectable" refers to a material having the characteristics required to administer a composition to a subject using an injectable device having a needle.

As used herein, the term "administering" refers to introducing the disclosure into a subject by any suitable method, and administration may be by a variety of routes, such as application, subcutaneous, dermal, vascular, biofilm, tissue fibers, synovial fluid, etc., so long as it can reach the target tissue. The dosage form may be used for, but is not limited to, topical application, subcutaneous injection, dermal injection, intravascular injection, intramuscular injection, intra-articular injection, intra-tendon injection, and intra-ligament injection. The ideal dosage of the compositions of the present disclosure may vary from subject to subject.

The tissue repair composition according to the present disclosure may exhibit a range of viscosities suitable for injection into the target tissue.

Furthermore, as used herein, the term "viscosity" refers to a property of a fluid, i.e., a flow having a viscosity, which is a resistance to flow. The viscosity can be expressed as viscosity, in particular complex viscosity (η·pa·s).

In any of the above embodiments, the tissue repair composition of the present disclosure may exhibit a complex viscosity of 1 Pa-s to 2,000 Pa-s, particularly ,5Pa·s～2,000Pa·s,8Pa·s～2,000Pa·s,1Pa·s～1,500Pa·s,5Pa·s～1,500Pa·s,8Pa·s～1,500Pa·s,1Pa·s～1,300Pa·s,5Pa·s～1,300Pa·s, or 8 Pa-s to 1,300 Pa-s.

The viscosity of the tissue repair composition used as a general biomaterial for tissue repair ranges from about 1pa·s or more to about 8,000pa·s or less. When the viscosity is within the above range, the composition can be naturally transplanted into an in vivo tissue after administration. Generally, when the viscosity of the composition for tissue repair is in the range of about 1pa·s or less, although it is implanted in the body, its ability to form its own shape is low, and thus the composition may not be able to generate a volume as a biomaterial for tissue repair, and it may be difficult to control the injection amount, for example, a large amount of injection liquid can be injected even with a small force. In addition, when the viscosity range is high, for example, about 8,000pa·s or more, it is difficult to extrude the syringe when injecting the composition into the body through the syringe, and excessive force may be required during the injection, so it is difficult to inject an accurate amount, and it is difficult to precisely control the injection amount, which may cause side effects.

The tissue repair composition of the present disclosure, when administered at a rate of 50mm/min, may be injected with an injection force of 0 or more and a compression force of about 60N, about 55N, about 50N, about 45N, about 40N, about 35N, about 30N, or about 25N or less. For example, the injection force described above may be injected through a 33 gauge needle, but is not limited thereto. In particular, setting the injection force below 40N may be appropriate according to approval and review guidelines for orthopaedic fillers.

The composition for tissue repair of the present disclosure may further include one or more compounds selected from the group consisting of anesthetic, vitamins, amino acids, metals, antioxidants, and mineral salts, but is not limited thereto.

The tissue repair composition of the present disclosure may further comprise any suitable adjuvant commonly used in the art, and such adjuvant may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffering agent, a stabilizing agent, or an isotonic agent, but is not limited thereto.

Another aspect of the present disclosure provides a biomaterial for tissue repair comprising the composition for tissue repair of the present disclosure.

The composition for tissue repair and the biomaterial for tissue repair are as described in other aspects.

Another aspect of the present disclosure provides a filler composition comprising a mixture of DNA fragments and an alcohol. In particular, the alcohol may be a polyol, more particularly a C3 or C4 polyol.

Further, the content of the DNA fragment mixture may be an amount of 2 to 5 wt% with respect to the total weight of the composition, and the content of the polyol may be an amount of 0.5 to 4 wt% with respect to the total weight of the composition.

As used herein, the term "filler", which is a material for tissue repair, refers to a medical device that is injected into the skin to restore volume, etc., and has the principle of maintaining the skin volume through physical repair.

The DNA fragment mixture, the polyol, etc. as described in other aspects, the filler composition may be a specific embodiment of the composition for tissue repair, and the description of the composition for tissue repair (DNA fragment mixture, polyol, content thereof, weight ratio, tissue moisturizing ability, liquid composition, injectate composition, application method, proper range of injection viscosity, etc.) of the present disclosure may be applied to the filler composition.

The filler composition of the present disclosure may further comprise one or more compounds selected from the group consisting of anesthetic agents, vitamins, amino acids, metals, antioxidants, and mineral salts, but is not limited thereto.

The filler composition of the present disclosure may further comprise any suitable adjuvant commonly used in the art, and such adjuvant may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffering agent, a stabilizing agent, or an isotonic agent, but is not limited thereto.

Another aspect of the present disclosure provides a method of repairing tissue, the method comprising the step of administering a tissue repair composition or a filler composition into a subject.

Application, tissue repair, compositions for tissue repair, filler compositions, and the like are described elsewhere.

As used herein, the term "subject" refers to all animals, such as rats, mice, livestock, etc., that require or are likely to require tissue repair, including humans. In particular, the subject may be a mammal, including a human.

Another aspect of the present disclosure provides a composition for use in tissue repair, the composition comprising a mixture of DNA fragments and a C3 or C4 polyol, wherein the mixture of DNA fragments is present in an amount of 2 wt% to 5 wt% relative to the total weight of the composition, and the polyol is present in an amount of 0.5 wt% to 4 wt% relative to the total weight of the composition.

The DNA fragment mixture, the polyol, the tissue repair, and the like are as described elsewhere.

[ Means for practicing the invention ]

Hereinafter, the present disclosure will be described in more detail by way of example embodiments. The following exemplary embodiments are merely illustrative of preferred embodiments of the present disclosure and are therefore not intended to limit the scope of the present disclosure in accordance therewith. Meanwhile, technical matters not described in the present specification may be fully understood and easily implemented by those skilled in the art of the present disclosure or the like.

Preparation example preparation of tissue repair biomaterial comprising a DNA fragment mixture and polyol

The DNA fragment mixture was added to a buffer and dissolved at a high temperature of 60 to 80℃using a hot stirrer to prepare a DNA fragment mixture solution. Adding the polyhydric alcohol into the DNA fragment mixture solution prepared at 60-80 ℃ in a hot stirrer, mixing, and then cooling the mixed solution to room temperature to prepare the liquid composition.

At this time, polynucleotides (PN; manufacturer: PHARMARESEARCH Co., ltd.) were used as representative examples of the DNA fragment mixtures, and the names and concentrations of the samples are shown in tables 1 and 2 below.

[ Table 1]

[ Table 2]

* Example 10 has the same composition and content as example 1.

Experimental example 1 verification of moisturizing Effect by animal experiments

A skin moisture loss model was prepared as a representative example using mouse tissue. At this time, a model is prepared with reference to a known method (Park,No-June,et al."Compound K improves skin barrier function by increasing SPINK5 expression."Journal of Ginseng Research44.6(2020):799-807).

The liquid composition prepared in the preparation example was injected into the body of the prepared animal model, and then a hydration measuring apparatus was used [ ]CM 825 (courage+ Khazaka electronic GmbH, germany)) measured the moisture content of the mouse skin at 25±5 ℃ and 50% ±5% rh.

As a result, as shown in fig. 1, it was confirmed that the examples including the mixture of glycerol and DNA fragments in specific amounts or ratios imparted higher hydration (moisturizing effect) to tissues.

In particular, it was confirmed that a composition comprising a mixture of DNA fragments in an amount of 2 wt% to 5wt% with respect to the total weight of the composition and a polyhydric alcohol in an amount of 0.5 wt% to 4 wt% with respect to the total weight of the composition has a critical significance for moisturizing effect, and as described below, it was also confirmed that the composition has excellent tissue repair effect in terms of viscosity, injection force, injection feeling, biodegradability and the like in the same content range, indicating that it is possible to obtain tissue repair effect with higher implantation rate and better moisturizing effect in the above-mentioned content combination range.

Experimental example 2 viscosity test

The complex viscosity (η, pas; hereinafter referred to as viscosity) was measured in the liquid compositions prepared in comparative examples 1 to 6 and examples 8 to 33 with respect to the mixture of DNA fragments alone, glycerol alone and the combination of the mixture of DNA fragments and glycerol, using a rheometer (NETZSCH (germany), kinexus Ultra + rheometer) at 48 hours after the preparation. Specifically, the viscosity is measured at a temperature of 25℃using a geometry of PU20, a gap of 1.0mm, a frequency of 0.1Hz, a shear strain of 0.5% and an analytical procedure of rSpace for Kinexus. The results are shown in Table 3 below.

[ Table 3]

As a result, as shown in table 3, it was confirmed that glycerol alone (comparative example 6) had a viscosity similar to that of purified water and thus could not be used for tissue repair, whereas the viscosity of the combination of the DNA fragment mixture and glycerol (examples 8 to 33) was reduced as compared with that of the DNA fragment mixture alone (comparative examples 1 to 5). This suggests that the ease of injection of the combination of the DNA fragment mixture and glycerol (examples 8 to 33) may be increased.

Experimental example 3 injection force test

The injection force was measured for comparative examples 1 to 5 and examples 8 to 33 except for glycerin alone (comparative example 6) which was verified as not being useful for tissue repair in experimental example 2.

The injection force represents the force (N) required to inject the injectable solution and is measured at an injection speed of 50mm/min. The liquid compositions prepared in examples and comparative examples for all checking injection force were measured using an injection force tester (tensile and compressive tester) at 48 hours after the preparation. Specifically, the injection force was measured using a tensile and compressive tester (universal tester (UTM), dahua tester, korea) under the conditions that the measurement temperature was 25.+ -. 2 ℃, the injection needle was JBP Korea (Korea), 33G nanoneedle, and the injection speed was 50mm/min. The results are shown in Table 4 and FIG. 2 below.

[ Table 4]

The injection force values of the glycerol-free compositions (comparative examples 1 to 5) were replaced with 100%, and the values of the examples were normalized to those of the comparative examples based on the same content of the DNA fragment mixture, and the results are shown as% values in fig. 2.

As a result, as shown in table 4 and fig. 2, it was confirmed that the injection force was reduced in the case of binding to glycerol as compared with the DNA fragment mixture alone, and that even though the comparative example had a higher injection force, the example having the combination of the DNA fragment mixture and glycerol had a higher injection force control effect.

Experimental example 4 injection sensation test

The injection feeling was evaluated for representative comparative examples and examples, excluding glycerin alone (comparative example 6) which was confirmed to be not useful for tissue repair in experimental example 2, and excluding examples 32 and 33 which did not satisfy the injection force prescribed in the plastic surgery filler approval guidelines, which should be set to 40N or less.

Blind tests were performed on independently enrolled experimenters (4 persons) who evaluate the injection sensation by releasing each composition of the comparative and experimental examples into a petri dish using a syringe needle (33-gauge nanoneedle) used in the actual product. All other conditions were the same as those in the injection force test except that a device (apparatus) for measuring injection force was used. Injection was easier (more comfortable) to get 1 score and difficult (more uncomfortable) to get 5 scores. The results are shown in tables 5 and 6 below. Table 5 shows the number of people scored for each score.

[ Table 5]

[ Table 6]

As shown in tables 5 and 6, in the case of combination with glycerol (example 8, etc.), the actual injection sensation test score was lower, indicating that the injection sensation was superior to that of the DNA fragment mixtures alone (comparative examples 1,2 and 4).

Experimental example 5 phase angle test

The phase angle (δ, °) of each of the liquid compositions prepared in examples and comparative examples was measured using a rheometer (NETZSCH (germany), kinexus Ultra + rheometer) 48 hours after preparation. Specifically, the phase angle was measured at a measured temperature of 25℃using the geometry PU20, gap 1.0mm, frequency 0.1Hz, shear strain 0.5% and analytical procedure rSpace for Kinexus. The results are shown in FIGS. 3 to 6.

As a result, as shown in fig. 3 to 6, the phase angle in the case of combination with glycerol (examples 8 to 31) was increased as compared with the DNA fragment mixture alone (comparative examples 1 and 4), which suggests that the ease of injection can be increased by further increasing the fluidity.

Experimental example 6 biodegradability of bioremediation material based on the presence and absence of DNA fragment mixture and polyol

Liquid compositions each comprising a mixture of DNA fragments and/or a polyol (glycerol, propylene glycol, butylene glycol) within the scope of comparative example 6 and example 28 were injected separately into mice. The mice used were SKH-1 hairless mice (6 week old, female) and were kept at a temperature of 22±2 ℃ and a relative humidity of 50±10%, with ad libitum feeding and water. The experimental period included a1 week acclimation period followed by sample injection, and euthanasia 60 hours after injection. A volume of 100. Mu.L was injected intradermally into the dorsal region of the mice. In addition, a change in volume at the injection site after sample injection was also observed. The examination result using 3D photo simulation (Primos, canfield (USA)) is shown in fig. 7.

As a result, as shown in fig. 7, it was confirmed that the polyhydric alcohol alone (glycerol, propylene glycol, butylene glycol) was completely decomposed immediately after injection and could not be used for tissue repair purposes. However, it was confirmed that even after 60 hours, the combination of the DNA fragment mixture and the polyhydric alcohol (glycerol, propylene glycol, butylene glycol) still exists, indicating that they are suitable as a biomaterial for repair.

Experimental example 7 comparison of the height and breadth after injection of liquid composition

When the tissue repair biomaterial spreads too widely after injection into the body, the repair effect may be small, and when the breadth is narrow and the height is high, it may be too prominent visually and aesthetically, causing problems such as lumps or urticaria. Thus, the breadth and height after injection were evaluated.

In this experiment, SKH-1 hairless mice (6 week old, female) were used. The mice were kept at a temperature of 22.+ -. 2 ℃ and a relative humidity of 50.+ -. 10% with ad libitum access to food and water. The experimental period included a1 week acclimation period followed by sample injection and measurement was performed immediately after injection. Mice were euthanized after 7 days. A volume of 100. Mu.L was injected intradermally into the dorsal region of the mice.

For this, each of the liquid compositions of the comparative examples and examples prepared in the preparation examples was injected into mice, and the height and breadth of the injected samples were measured using a vernier caliper (MITUTOYO, japan) and analyzed using ImageJ software, and the results are shown in fig. 8 and table 7.

[ Table 7]

As shown in table 7 and fig. 8, the tested examples 14, 15, 16 and 18 were confirmed to have similar repair field levels as the commercial products (Rejuran; RJR; PHARMARESEARCH co., ltd.) indicating that the compositions of the present disclosure have excellent tissue repair effects.

Experimental example 8 comparison of the efficacy of other polyols

In order to compare the efficacy between example 1 prepared using glycerol and examples 2-7 prepared using other polyols instead of glycerol, their properties were compared and are shown in fig. 9.

As a result, as shown in fig. 9, examples 4 to 6 using other polyols produced a large amount of foam during the preparation of the liquid composition, which may increase the probability of defective products in the future production of products, confirming that they cannot be used as materials for tissue repair.

Further, the results of evaluating the complex viscosity in the same manner as in experimental examples 2 of examples 1 to 3 and 7 and purified water without generating foam are shown in table 8 below.

[ Table 8]

As a result, as shown in table 8, it was confirmed that example 7 could not be used as a biomaterial for tissue repair because its viscosity was almost as low as the level of purified water.

From the above results, it was confirmed that the composition for tissue repair comprising the DNA fragment mixture and the polyhydric alcohol of the present disclosure has not only an excellent tissue repair effect but also a moisturizing effect in a combination of specific content ranges. These results indicate that the composition does not excessively absorb water in the surrounding tissue at the time of injection, but provides water to the surrounding tissue, thus not causing the surrounding tissue to dry, but rather alleviating dryness, and has a high implantation rate and a good moisturizing effect.

Based on the foregoing description one skilled in the art will appreciate that the present disclosure may be embodied in different specific forms without changing its technical spirit or essential characteristics. In this respect, it should be understood that the above-described embodiments are not limiting, but are illustrative in all aspects. The scope of the disclosure is defined by the appended claims, rather than by the description preceding them, and therefore, the scope of the claims and all changes and modifications that fall within this scope, or equivalents of such scope, are intended to be embraced by the claims.

Claims (9)

1. A composition for tissue repair, the composition comprising:

DNA fragment mixture, and

A C3 or C4 polyol,

Wherein the method comprises the steps of

The content of the DNA fragment mixture is 2-5 wt% relative to the total weight of the composition,

The content of the polyol is 0.5 to 4wt% relative to the total weight of the composition, and

The polyol is any one or more selected from the group consisting of glycerol, propylene glycol and butylene glycol.

2. The composition for tissue repair according to claim 1, wherein the composition has tissue moisturizing ability.

3. The composition for tissue repair of claim 1, wherein the composition increases the moisture content of tissue when injected into the tissue.

4. The composition for tissue repair according to claim 1, wherein the weight ratio of the DNA fragment mixture to the polyhydric alcohol is 10:1 to 1:2.

5. The composition for tissue repair according to claim 1, wherein the weight ratio of the DNA fragment mixture to the polyhydric alcohol is 6:1 to 1:1.

6. The composition for tissue repair according to claim 1, wherein the DNA fragment mixture is a Polynucleotide (PN), a Polydeoxyribonucleotide (PDRN), or a mixture thereof.

7. The composition for tissue repair according to claim 1, wherein the molecular weight of the DNA fragment mixture is 50kDa to 10,000kDa.

8. A biomaterial for tissue repair comprising the composition according to any one of claims 1 to 7.

9. A filler composition comprising:

DNA fragment mixture, and

A C3 or C4 polyol,

Wherein the method comprises the steps of

The content of the DNA fragment mixture is 2-5 wt% relative to the total weight of the composition,

The content of the polyol is 0.5 to 4wt% relative to the total weight of the composition, and

The polyol is any one or more selected from the group consisting of glycerol, propylene glycol and butylene glycol.